Berardinelli type lipodystrophy is one of the genetic lipodystrophies. In this disease, fat tissue cannot be formed. Because lipodystrophy is associated with treatment-resistant diabetes, the prognosis of this disease is not good.
What is Berardinelli-type lipodystrophy?
Berardinelli-type lipodystrophy is outwardly the exact opposite of obesity. While obesity causes too much fat to be stored in adipose tissue, in this condition the body is unable to either make or store fat at all. Normally, obesity is thought to be a prerequisite for type 2 diabetes. However, diabetes always occurs in Berardinelli type lipodystrophy, which is even resistant to therapy. There is also a disturbed lipid metabolism, which produces very high blood lipid levels. The prognosis of this disease depends on the sequelae of diabetes. Lipodystrophy can be hereditary or acquired. Most forms of this heterogeneous group of diseases are a consequence of other diseases and thus acquired. For example, antiretroviral treatment for HIV can lead to a severe disturbance of lipid metabolism with extensive loss of adipose tissue. However, Berardinelli-type lipodystrophy is genetic. Although genetically caused lipodystrophies are very rare, they too can be classified into several types. This lipodystrophy is also known synonymously as Berardinelli-Seip congenital lipodystrophy (BSCL) or congenital generalized lipodystrophy (CGL). Four types have been described to date for BSCL, all of which are inherited in an autosomal recessive manner.
Causes
Basically, all types of BSCL are caused by gene mutations that encode enzymes for fat synthesis or fat storage. Type 1 represents the most common form of BSCL. This is a mutation of the gene AGPAT2. This gene codes for the enzyme acyltransferase, which is responsible for the transfer of fatty acids as part of an intermediate step in fat synthesis. Disruption of this transfer inhibits fat synthesis. Type 2 of BSCL is caused by a genetic alteration of the gene BSCL2, which encodes the enzyme seipin. Seipin assists in the formation of lipid droplets in the endoplasmic reticulum and their storage within the cell. Types 3 and 4 of BSCL are caused by mutations in genes responsible for the formation and function of caveolae (small indentations of plasma membranes). Caveolae serve to store cholesterol-containing lipids in muscle and fat cells. The disruption of fat synthesis and storage initially results in the absence of adipose tissue in BSCL. Thus, supplied fats and carbohydrates cannot be fully utilized. Insulin is supposed to ensure that glucose is channelled into the cells for energy production and storage. Due to the lack of fat incorporation in fat and muscle cells, fewer receptors for insulin are also formed. Despite high insulin concentrations, the blood glucose level can therefore not be lowered. At the same time, blood fats and fatty acids also accumulate in the blood because they cannot be stored in the fatty tissue and muscles. High blood glucose and blood fat levels lead to the typical manifestations of the metabolic syndrome. High concentrations of growth hormone cause giant growth, increased muscle development, and acromegaly.
Symptoms, complaints, and signs
Berardinelli-type lipodystrophy is characterized by absent adipose tissue, high blood glucose levels, and high blood lipid levels. The abnormal values are difficult to control. Giant growth, thickening of the epidermis, ovarian changes, and severe muscle hypertrophy (strengthening of muscles) are also observed. Furthermore, hypertrophic cardiomyopathy, fatty liver and hormonal disorders may occur. The hormonal disorders manifest as accelerated growth, premature puberty, or muscle hypertrophies. Acromegaly can also occur. In this case, the so-called acra (protruding parts of the extremities and body) such as hands, fingers, feet, toes, ears, chin, nose, penis, breast and others enlarge. Bone cysts often develop with increased risk of fracture. In addition, there is usually mental retardation.Furthermore, those affected suffer from a metabolic syndrome that is difficult to treat. The prognosis is largely dependent on the sequelae of diabetes and impaired lipid metabolism.
Diagnosis and disease progression
The diagnosis of Berardinelli-type lipodystrophy can be made on the basis of symptoms, laboratory findings, imaging of an accelerated-growing skeletal system, and genetic testing.
Complications
First and foremost, Berardinelli-type lipodystrophy results in elevated blood lipids and also elevated blood glucose levels. These complaints have a very negative impact on the patient’s health and in most cases lead to a significantly reduced life expectancy. Furthermore, those affected suffer from excessively strong muscles, which is not infrequently accompanied by an unusual appearance. Likewise, lipodystrophy of the Berardinelli type leads to the development of a fatty liver and thus to various hormonal disorders in the patient. Consequently, puberty occurs at an early age, resulting in disturbed development of the patient. Furthermore, various parts of the body of the affected person are affected by a giant growth, so that various restrictions in the daily life of the affected person can occur. The patient’s quality of life is significantly reduced by Berardinelli type lipodystrophy. It is also not uncommon for the parents and relatives to suffer from psychological discomfort and depression. Mental retardation also usually occurs, so that in most cases the patients are dependent on the help of other people. Since a causal treatment of Berardinelli-type lipodystrophy is not possible, patients are dependent on various therapies designed to improve their quality of life. Usually, no complications occur during this process.
When should you see a doctor?
If no formation of adipose tissue is observed with a balanced and good diet, a follow-up visit to a physician is recommended. If there are other abnormalities or irregularities of the connective tissue or the general appearance of the skin, the observations should be discussed with a doctor. If the child grows particularly fast in direct comparison to children of the same age, a visit to the doctor is advisable. This also applies in case of thickening of the upper skin layer. Irregularities of the female menstrual cycle or behavioral abnormalities should be discussed with a doctor. In case of hormonal peculiarities, premature puberty and enlarged limbs, a visit to the doctor is advisable. Visual irregularities of the physique, protruding hands, feet, fingers or toes are indications of a present disease. A visit to the doctor is necessary so that the cause can be clarified. In case of visual peculiarities of the ears, chin, nose as well as the chest, the observations should be discussed with a doctor. If irregularities of the bone structure can be detected, if there is a formation of cysts, swellings and ulcers or if movement problems set in, a doctor must be consulted. If there is a susceptibility to fractures, consultation with a physician is advised.
Treatment and therapy
There is no causative treatment for Berardinelli-type lipodystrophy. To date, there are also no drugs that would be able to positively influence the disturbances in fat synthesis. The diabetes is difficult to treat. Insulin doses do not help because of the extreme insulin resistance. There is enough insulin available. However, it cannot have any effect because of the lack of insulin receptors. It is also difficult to lower the high blood lipid levels. The diabetes and the high blood fat values make a low-fat and low-carbohydrate diet necessary. Of course, constant medical control is necessary to keep the consequential damages of diabetes as low as possible. Nevertheless, the prognosis is not good at present.
Outlook and prognosis
Patients with Berardinelli-type lipodystrophy usually receive an unfavorable prognosis from the treating physician. The cause of the disorder cannot and may not be corrected with current medical options. There is a genetic disposition which, for legal reasons, may not currently be altered. The therapy of the affected person is therefore aimed at alleviating the existing symptoms and improving the quality of life. The disease is associated with numerous adversities, which represent an enormous burden for the patient as well as his relatives.In addition to visual abnormalities, mental impairments are to be expected. Nevertheless, it must be taken into account that the gene mutation always shows itself individually in its intensity. Each sufferer therefore shows different symptoms, but not all are developed to the same degree. In addition, how the patient deals with the disease is an important factor in the course of the disease. Psychological secondary disorders can occur, which have an additional negative effect on development. The earlier treatment is initiated, the better the further prospects often are. Despite all efforts, the patient is dependent on the help and support of other people for the rest of his life. He often needs daily nursing and medical care in addition to the cooperation of relatives. Independent daily living is not possible with this disease.
Prevention
Berardinelli-type lipodystrophy is a genetic disease that is inherited in an autosomal recessive manner. Therefore, prevention of this disease is not possible. However, in cases of familial clustering of lipodystrophies, human genetic counseling and testing can help assess the risk to offspring. If both parents each have the mutated gene once, there is a 25 percent chance that the offspring will develop this form of lipodystrophy.
Follow-up
Because lipodystrophy is a serious disease that cannot cure itself, aftercare focuses on managing the disease well, both physically and mentally. In most cases, those affected by lipodystrophy suffer from diabetes, which requires regular check-ups with the attending physician. Due to the psychological strain associated with the disease, those affected sometimes develop depression or psychological upsets. This can also occur in parents or relatives. It can help to clarify this with a psychologist and to weigh up the need for therapy. The further course depends on the individual condition of the person affected and cannot be predicted in general. In many cases, however, the life expectancy of the affected person is significantly limited by this disease.
What you can do yourself
Berardinelli-type lipodystrophy is difficult to treat and is associated with a comparatively poor prognosis. The emotional burden for those affected and their relatives is correspondingly great. If possible, patients spend time in care facilities, where social contacts sometimes have a positive effect on the quality of life of those affected. Since the disease is often associated with mental retardation, adequate care promotes the patient’s condition. Although medication against Berardinelli’s lipodystrophy is hardly effective, close monitoring by various physicians is still necessary. This is because diabetes causes secondary damage that must be treated appropriately. For the patients’ quality of life, it is important that they actively participate in the medical therapy and take the drugs as prescribed. In order not to negatively influence the high blood lipid values, patients adhere to a diet that contains only few fats and carbohydrates. In this context, advice and support from a nutritionist is essential, who, together with the specialist, draws up an individual diet plan for the patient. Psychotherapy supports the patient and parents in dealing with the disease.
